Ziel
The goal of this project is to study the mechanisms underlying the modulation by second messengers of nicotinic acetylcholine receptor (nAChR)-activated ionic channels in muscle, in neurons of invertebrates (snail) and in vertebrates (sympathetic ganglion of the rat).
A combination of the following techniques will be used: electrophysiology (patch-clamp, microelectrode, and intracellular dialysis recording); chemistry (synthesis of new nACh receptor-channel modulators); and fluorescence image analysis (confocal laser scanning microscopy).
The following areas will be investigated: the comparative properties of whole-cell AChR-activated currents in mouse myotubes and in sympathetic ganglia neurons; modulation of nAChR by four protein kinase systems (cAMP- and cGMP-dependent phosphorylation; the protein kinase C- and tyrosine kinase-dependent phosphorylation); the modulation of ACh-activated currents in snail neurons by cytoskeleton; the pathways involved in intracellular Ca 2+ ([Ca 2+]i) elevation at AChR-activation and the modulation of AChR channels by [Ca 2+]i.
This study will make it possible to elucidate mechanisms of nAChR channels modulation by intracellular phosphorylation and by the state of neuronal cytoskeleton.
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75674 Paris 14
Frankreich